Effects of endurance exercise training on inflammatory circulating progenitor cell content in lean and obese adults

Abstract

Key points: Chronic inflammation underlies many of the health decrements associated with obesity. Circulating progenitor cells can sense and respond to inflammatory stimuli, increasing the local inflammatory response within tissues. Here we show that 6 weeks of endurance exercise training significantly decreases inflammatory circulating progenitor cells in obese adults. These findings provide novel cellular mechanisms for the beneficial effects of exercise in obese adults.

Abstract: Circulating progenitor cells (CPCs) and subpopulations are normally found in the bone marrow, but can migrate to peripheral tissues to participate in local inflammation and/or remodelling. The purpose of this study was to compare the CPC response, particularly the inflammatory-primed haematopoietic stem and progenitor (HSPC) subpopulation, to a 6 week endurance exercise training (EET) intervention between lean and obese adults. Seventeen healthy weight (age: 23.9 ± 5.4 years, body mass index (BMI): 22.0 ± 2.6 kg m^-2 ) and 10 obese (age: 29.0 ± 8.0 years, BMI: 33.1 ± 6.0 kg m^-2 ) previously sedentary adults participated in an EET. Blood was collected before and after EET for quantification of CPCs and subpopulations via flow cytometry, colony forming unit assays and plasma concentrations of C-X-C motif chemokine 12 (CXCL12), granulocyte-colony stimulating factor (G-CSF), and chemokine (C-C motif) ligand 2 (CCL2). Exercise training reduced the number of circulating HSPCs and adipose tissue-derived mesenchymal stem cells (AT-MSCs). EET increased the colony forming potential of granulocytes and macrophages irrespective of BMI. EET reduced the number of HSPCs expressing the chemokine receptor CCR2 and the pro-inflammatory marker TLR4. EET-induced changes in adipose tissue-derived MSCs and bone marrow-derived MSCs were negatively related to changes in absolute fitness. Our results indicate that EET, regardless of BMI status, decreases CPCs and subpopulations, particularly those primed for contribution to tissue inflammation.

Keywords: Hematopoietic stem cells; Inflammation; Mesenchymal stem cell; Obesity; chemokine c receptor 2.

Figure 1. Colony forming unit potential of innate immune populations are elevated during obesity and responsive to EET

A, CFU‐Gs are elevated in in obese adults but unaffected by EET (^amain effect of group). B, CFU‐Ms are not changed by exercise nor different between BMI classes. C, CFU‐GMs are elevated in obese participants (main effect of group) and increase as a result of EET in both BMI classes (main effect of exercise). D, total CFU colonies trended higher in obese adults and are increased by EET irrespective of BMI status (main effect of exercise). ^* P < 0.05; ^a P < 0.05; n = 17 Lean, n = 9 Obese; data are presented as means ± SD.

Figure 2. EET modifies CCR2 and TLR4 expression on HSPCs

A, the concentration CCR2⁺ HSPCs in isolated PBMCs was significantly decreased in both groups as a result of 6 weeks of EET (main effects of exercise). B, CCR2 content (expressed as median fluorescence intensity: MFI) was significantly decreased after 6 weeks of EET in both groups (main effect of exercise). C, the percentage of HSPCs expressing CCR2 was significantly decreased in the obese (group × time interaction), but not lean, group as a result of 6 weeks of EET. D, the concentration of HSPCs expressing TLR4 in isolated PBMCs was decreased after 6 weeks of EET in both lean and obese adults (main effect of exercise). E, TLR4 content (expressed as median fluorescence intensity: MFI) was significantly increased in both lean and obese adults after 6 weeks of EET. F, the percentage of HSPCs expressing TLR4 was not changed with 6 weeks of EET in lean or obese adults. ^* P < 0.05; n = 17 Lean, n = 10 Obese; data are presented as means ± SD.

Figure 3. EET attenuates circulating CPC mobilization factors

A, CXCL12 levels declined in lean, but not obese, participants as a result of EET training (group × time interaction). B, G‐CSF showed a trend to be decreased in the obese group as a result of the EET (group × time interaction). C, CCL2 was not altered after 6 weeks of EET. ^* P < 0.05; n = 17 Lean, n = 10 Obese; data are presented as means ± SD.

Figure 4. Baseline fitness is positively related to baseline proportions of HSPCs, and changes in AT‐MSCs and BM‐MSCs are negatively related to changes in absolute fitness

A, the proportion of HSPCs is positively related to baseline absolute ${\dot{V}}_{{\mathrm{O}}_2}$ (ρ = 0.432). ^* P < 0.05; n = 25. B, the change in AT‐MSC content in isolated PBMCs from EET was negatively related to changes in absolute ${\dot{V}}_{{\mathrm{O}}_2}$ (ρ = −0.52; P < 0.05); n = 25. C, the change in BM‐MSC content in isolated PBMCs from EET was negatively related to changes in absolute ${\dot{V}}_{{\mathrm{O}}_2}$ (ρ = −0.41; P < 0.05). n = 25.